System for non-perturbative sampling of sample-volume-limited bioreactors

The system addresses the challenge of non-perturbative sampling in small bioreactors by controlling inflow and outflow rates and gas exchange to maintain stable conditions, facilitating accurate metabolic and gene expression analysis.

US20260002112A1Pending Publication Date: 2026-01-01VANDERBILT UNIV
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Patent Information

Application Number
US19/323144
Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Priority Date
2022-12-02
Filing Date
2025-09-09
Publication Date
2026-01-01

AI Technical Summary

Technical Problem

Current bioreactor technologies face challenges in non-perturbatively sampling and maintaining the microenvironment of small volume-limited bioreactors, leading to significant volume changes and metabolic disruptions during sample removal, which affect the accuracy of metabolic and gene expression analysis.

Method used

A system with controlled input and output pumps and a controller manages bioreactor parameters to maintain a stable microenvironment during sample accumulation, storage, and withdrawal, ensuring minimal perturbation by adjusting inflow and outflow rates and gas exchange to mimic chemostatic conditions.

Benefits of technology

Enables accurate and non-perturbative sampling from small bioreactors, maintaining consistent metabolic conditions, allowing for rapid and efficient analysis of multiple samples without disrupting the bioreactor environment.

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Abstract

A non-perturbative sampling system includes a bioreactor comprising a chamber containing media with cells; an input tube for delivering nutrient-laden media to the chamber; and an output tube for withdrawing a sample from the chamber; an input pump configured to deliver the nutrient-laden media at an inflow rate; an output pump configured to withdraw the sample at an outflow rate; and a controller configured to operate the input and output pumps to regulate the inflow and outflow rates, respectively, such that the bioreactor is a variable-volume bioreactor in which an instantaneous volume of media either varies continuously with time or is held constant, and operable in sample accumulation phase, sample storage phase, sample withdrawal phase, or volume restoration phase, to maintain the quantity of nutrients per cell within the media in the chamber unchanged. The sample withdrawal phase either follows the sample accumulation phase or precedes the volume restoration phase.
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